Chelating agents are used extensively in, for example, the chemical industry, the mining industry, in medicine and in analytical research applications. For example, EDTA (Ethylenediamine tetraacetic acid) has been used to analyze for a number of transition metals. The structurally related imidodiacetic acid has been used to analyze for divalent metals such as calcium and cadmium.
Imidodiacetic acid is often used in industrial applications in a polymer bound form. The polymer bound forms include ion-exchange resins sold under the trademarks Amberlite IRC 718.TM., Dowex Al.TM., and Chelex 100.TM., all of which are suitable for industrial applications and all of which are essentially imidodiacetic acid attached to an insoluble polymer support.
In using carboxylate ions for the binding of metals, binding is effected when the electron pairs of the oxygens are donated to the outer orbital of the metal ion moiety. It has been shown that the distal electron pairs of the oxygen atoms are more basic than the proximal electron pairs. The drawing below is illustrative of this concept. ##STR1## See, R. D. Gandour, "On the Importance of Orientation in General Base Catalysis by Carboxylate." Bioorganic Chemistry, 10, 169-176 (1981).
In known chelating agents which employ carboxylate groups to bind metal ions--such as imido diacetate, dipicolinate and EDTA--generally only the proximal, less basic electron pairs are involved in binding the metals. Better metal ion binding would occur with a chelating agent which involves the more basic, distal, electron pairs of the oxygen atoms of a carboxylate group. Chelating agents also exist which employ as the active, binding functions, groups other than carboxylates--such groups include nitriles, thiol acids, amides, amidines, dithio acids, and hydroxamic acids. In these known chelating agents, as well as in imido diacetate, dipicolinate and EDTA, the active functions are generally not rigidly held in an optimal position for chelation, but rather will usually be freely rotatable such that they rotate through many positions where chelation cannot occur. Thus, the probability of metal binding is relatively low and the rate of metal binding is relatively slow and inefficient.
The recently discovered compound, cis-cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, has been shown to prefer to exist, and to be more stable, in the conformation: ##STR2## rather than the other possible conformation: ##STR3## See, D. S. Kemp and K. S. Petrakis "Synthesis and Conformational Analysis of cis, cis, 1,3,5-Trimethylcyclohexane-1,3,5-Tricarboxylic Acid," J. Org. Chem., 46, 5140-5143 (1981). Kemp and Petrakis have demonstrated that the methyl groups of this compound force a conformation in which any two of the carboxyl groups are rigidly maintained in the "C" shape illustrated above by the darkened lines in compound A. This shape is rigidly maintained in derivatives of compound A such as the acid chloride anhydride, which is one of the compounds from which the compounds of the invention are made, and has the structure; ##STR4## The shape illustrated by the darkened lines of compound A is also rigidly maintained in the imide bonded groups which are formed following reaction of compound C with a substituted or unsubstituted, fused or monocyclic, five or six membered diamine, wherein the amine groups have a 1,3 relationship. This reactions forms the compounds of the invention.
It is therefore an object of the invention to provide a chelating agent which can rigidly orient the active functions and preferably prevent rotation of the active functions through positions at which effective binding does not occur. It is a further object of the invention to provide a method of utilizing the compounds of the invention as effective chelating agents.